Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital, and Institute of Immunology, Jilin University, Changchun, China.
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA.
Nat Commun. 2020 Jan 29;11(1):581. doi: 10.1038/s41467-019-14102-4.
Cancer cells are poorly immunogenic and have a wide range of mutations, which makes them unsuitable for use in vaccination treatment. Here, we show that elimination of CD47, a ligand for the myeloid cell inhibitory receptor SIRPα, from tumor cells by genetic deletion or antibody blocking, significantly improves the effectiveness of the immune response to tumour cells. In both solid and hematopoietic mouse tumor models, vaccination with tumor cells or tumor antigen-expressing cells, that lack CD47 or were pre-coated with anti-CD47 antibodies, achieved an antitumor immune response. The efficacy of this approach was synergistically enhanced when used in combination with anti-PD-1 antibodies. The induction of antitumor responses depends on SIRPαCD11c DCs, which exhibit rapid expansion following introduction of CD47-deficient tumor cells. Our results indicate that CD47-deficient whole tumor cells can induce antitumor responses.
癌细胞免疫原性差，且突变广泛，因此不适合用于疫苗治疗。在这里，我们表明通过基因缺失或抗体阻断从肿瘤细胞中消除 CD47（一种髓系细胞抑制性受体 SIRPα 的配体），可显著提高对肿瘤细胞免疫反应的有效性。在实体瘤和造血鼠肿瘤模型中，用缺乏 CD47 或预先用抗 CD47 抗体包被的肿瘤细胞或肿瘤抗原表达细胞进行疫苗接种，可实现抗肿瘤免疫反应。当与抗 PD-1 抗体联合使用时，该方法的疗效得到协同增强。抗肿瘤反应的诱导取决于 SIRPαCD11c DC，其在引入缺乏 CD47 的肿瘤细胞后迅速扩增。我们的结果表明，缺乏 CD47 的整个肿瘤细胞可诱导抗肿瘤反应。
